As disclosed in U.S. Pat. No. 4,588,587, of common assignment herewith, the saliva of blood sucking animals such as leeches, possesses anticoagulant activity. As also discussed in the above-referenced patent, an extract of certain leech salivary glands also exhibits antimetastatic effects. It has been postulated that these effects may result from a unique and complex combination of anticoagulants, and/or protease inhibitors, and/or other constituents of the extract which act synergistically.
The theoretical mechanism by which metastasis occurs is believed to involve several steps, such as entry of tumor cells into the organisms circulation (intravasculation); their transport by the blood stream; interactions of circulating malignant cells with platelets and plasma clotting factors with activation of the hemostatic system; interaction of the same cells with host cells other than platelets; arrest of tumor cells, surrounded by platelet aggregates and fibrin clots within capillaries; proteolytic attack of the blood vessel wall, particularly of its basement membrane, by tumor enzymes; escape from the circulation system (extravasculation); and formation of secondary tumors or colonies.
Crucial to this mechanism is the ability of the circulating tumor cell to initiate the formation of a blood clot which serves to lock the cell in a capillary. Falanga, et al (Biochemistry 24:5558-5567, 1985) isolated and characterized a particular cancer procoagulant which was shown to initiate coagulation through activation of factor X. In addition, other researchers cited in that reference have isolated cancer procoagulants which directly activate factor X. Finally, one of the present inventors' prior publications (Cancer Metastasis Reviews 3, 99-116 (1984) presents a summary of research into the activation of the coagulation system by tumor cells, which also discusses the possible involvement of factor X.